Alcohol and GABA: ethanol intake modifies hippocampal nipecotic acid binding in ethanol-preferring and non-preferring rats.
3H-nipecotic acid (3H-NIP) binding to GABA uptake recognition sites was studied in the hippocampus of 3 groups of male, Long Evans rats: Group 1: ethanol-naive rats (ENR); Group II: ethanol-preferring rats (DR) and non-preferring rats (NDR), which had consumed about 5 g.kg-1.d-1 and 1 g-1.d-1 of alcohol respectively in the form of a 12% ethanol solution prior to 3H-NIP binding analysis; Group III: DR and NDR who had had no access to ethanol for 21 d after the initial exposure of ethanol solution (28 d). Binding studies showed that ethanol drunk by both DR and NDR in Group II decreased 3H-NIP binding (Bmax decreased) with an enhancement of affinity (KD decreased). In rats subjected to withdrawal of ethanol (Group III), affinity of 3H-NIP for GABA uptake sites was higher than in controls (Group I), but lower than in Group II, Bmax in this group being higher than in the 2 other groups. In Group III, KD was higher in DR than in NDR. These results showed that ethanol intake, in a free-choice paradigm, altered 3H-NIP binding, and that differences in ethanol intake between DR and NDR were associated with differences in sensitivity of hippocampal GABA uptake sites. These differences in 3H-NIP binding could either precede ethanol intake, or be a direct result from it. The results, together with data from other laboratories suggest that: 1), 3H-NIP binding sites are involved in the regulation of ethanol intake; 2), 1 factor responsible for individual differences in ethanol response is reflected by the GABA uptake system.
Daoust
M
M
Pharmacochimie, Faculty of Medicine of Rouen, Saint-Etienne-du-Rouvray, France.
Saligaut
C
C
Moore
N
N
Lhuintre
J P
JP
Boismare
F
F
D000818:Animals; D000431:Ethanol / Q000008:administration & dosage / Q000378:metabolism* / Q000494:pharmacology; D018756:GABA Antagonists; D006624:Hippocampus / Q000187:drug effects / Q000378:metabolism*; D008297:Male; D009557:Nipecotic Acids / Q000378:metabolism*; D011392:Proline / Q000031:analogs & derivatives*; D051381:Rats; D012646:Self Administration; D005680:gamma-Aminobutyric Acid / Q000378:metabolism*
D018756:GABA Antagonists; D009557:Nipecotic Acids; C030278:nipecotic acid; D000431:Ethanol; D005680:gamma-Aminobutyric Acid; D011392:Proline; C010983:homoproline